Patients with locally advanced unresectable or metastatic EGFR mutant non squamous cell non-small cell lung cancer
Conditions
Interventions
Phase 1 phase 2: telisotuzumab adizutecan 2.4 mg/kg Q3W plus osimertinib:telisotuzumab adizutecan 2.4 mg/kg Q3W plus osimertinib
telisotuzumab adizutecan (optimal dose) plus osimertinib:telisotuzumab adizutecan (optimal dose) plus osimertinib
Phase 1 phase 2: telisotuzumab adizutecan 1.6 mg/kg Q3W plus osimertinib:telisotuzumab adizutecan 1.6 mg/kg Q3W plus osimertinib
Phase 1 Phase 2: Osimertinib monotherapy:Osimertinib monotherapy
Stand of Care (SOC):Stand of Care (SOC)
Phase 1 Phase 2: telisotuzumab adizutecan 2.0 mg/kg Q3W+ osimertinib:Phase 1 Phase 2: telisotuzumab adizutecan 2.0 mg/kg Q3W+ osimertinib
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Before starting any screening or research specific procedure, the subject or their legal representative must voluntarily sign and date the IEC/IRB approved informed consent form; 2. Adults who are over 18 years old (or the acceptable age specified by local regulations, whichever is older); 3. Willing and able to comply with the procedures stipulated in this plan; 4.During the screening period and on the first day of the first cycle before treatment administration, the physical fitness status (PS) score of the Eastern Cooperative Oncology Group (ECOG) in the United States was 0 or 1; 5.During the screening period and on the first day of the first cycle before administering the study treatment, laboratory test values meet the following criteria: ?Within 7 days before administration on the first day of the first cycle, serum ALT and AST levels should be = 30 mL/min (Section 16, Appendix D); ?Total bilirubin = 1500/µ L and G-CSF was not used; ?Platelet count >= 100000/µ L and no platelet transfusion within 14 days before administration on the first day of the first cycle; ?Hemoglobin >= 9 g/dL (RBC not infused within 14 days before administration on the first day of the first cycle); ?Albumin >= 3 g/dL. 6. Participants must not be imprisoned and must voluntarily and be able to provide informed consent. Subjects who are unable to voluntarily provide informed consent include some adults who are protected by law (such as those under guardianship/assistance) or unable to express their wishes, as well as some adults receiving psychiatric treatment. At the discretion of the researchers, such patients may be included in the study; 7. All subjects must agree to provide recently collected FFPE tumor tissue (preferably collected during or after local late stage or metastatic disease diagnosis) or archived tissue for c-Met IHC detection and study stratification during the screening period. Random grouping (dose optimization queue) can only be performed after obtaining the c-Met IHC test results. Disease/illness activity level; 8. Have not received EGFR TKI treatment for locally advanced and/or metastatic diseases in the past (allowed to participate before C1D1)Except for research cases. For subjects who have previously received EGFR TKI adjuvant therapy, as long as the medication has been discontinued for = 12 months before the first day of the first cycle (e.g. since the last administration of osimertinib adjuvant therapy), they are allowed to be enrolled; 9.According to RECIST version 1.1, subjects must have at least one measurable lesion that has not received radiation therapy. If there is only one measurable lesion, as long as it has not received radiation therapy in the past and has not undergone biopsy within 14 days before the baseline tumor assessment scan, it can be used as the target lesion; 10. Suffering from metastatic/locally advanced non squamous cell NSCLC confirmed by histology or cytology, and treated according to the standards of the CLIA accredited laboratory (US research center) or officially reco
Exclusion criteria
Exclusion criteria: 1. There is a history of interstitial lung disease (ILD) requiring systemic hormone therapy, non infectious inflammation of the lungs, or Chest CT scan during screening suggests any evidence of active ILD/non infectious inflammation in the lungs; 2. Presence of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), and drug-induced pulmonary inflammation History of symptoms or idiopathic pulmonary inflammation; 3. There is a clinically significant (according to the researcher's assessment) history of accompanying lung specific diseases, including but not limited to: ? Basic pulmonary diseases (i.e. pulmonary embolism [within 3 months prior to enrollment], severe asthma, severe COPD, restrictive pulmonary disease, pleural effusion, dependence on auxiliary oxygen supply, etc.). ?During screening, there may be any autoimmune disease, connective tissue disease, or inflammatory disease, accompanied by confirmed or suspected lung involvement (i.e. rheumatoid arthritis, Sjogren's syndrome, sarcomatosis, etc.), as well as a history of total lung resection; 4. It is known that there is active/symptomatic CNS metastasis and/or cancerous meningitis. Subjects who have received previous treatment for brain metastases are allowed to be enrolled, provided that imaging review shows imaging stability (i.e., no evidence of progression) for at least 4 weeks (note: imaging review should be conducted before C1D1), clinical stability, and no need for hormone therapy for at least 14 days prior to the first dose of study treatment. For asymptomatic subjects with brain metastases, if the researcher determines that curative treatment is not necessary, they are allowed to be enrolled. CNS metastasis radiotherapy is not allowed within 14 days before the study treatment; 5. The subject has leptomeningeal disease or spinal cord compression that cannot be cured by surgery or radiation therapy; 6. Any history of malignant tumors, except for malignant tumors that have received curative treatment, have no known active disease within 2 years before the first administration of the study treatment, and have a low risk of recurrence as determined by the researcher, as well as successfully treated non melanoma skin cancer or local cervical carcinoma in situ; 7. There has been a clinically significant (at the discretion of the researcher) history of drug or alcohol abuse within the past 6 months; 8. There are diseases that may interfere with drug absorption, including but not limited to short bowel syndrome; 9. There is a clinically significant history of disease, or any other reason that the researcher determines may interfere with the subject's participation in this study or make the subject unsuitable for receiving study treatment; 10. Have undergone major surgery or suffered severe traumatic injury within 28 days prior to any study treatment, or are expected to require major surgery during the study intervention process. Subjects who undergo vascular access device implantation or tumor biopsy within 28 days prior to treatment are allowed to be enrolled; 11. There are conditions that hinder the full absorption of osimertinib, such as intractable nausea and vomiting, chronic gastrointestinal diseases, inability to swallow drug preparations, or previous major intestinal resection surgery; 12. Have experienced allergic reactions or significant sensitivity to the ingredients of research drugs (and their excipients) and/or other similar products
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);Progression free survival (PFS) (Phase III); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival (Phase II);Duration of Response (DoR) (Phase II);Disease control rate DCR (phase II);Overall survival OS (Phase II);Overall survival OS (Phase III);Objective response rate or, duration of response dor, disease control rate DCR (Phase III);PRO assessment: changes in physical function from baseline, lung cancer symptoms from baseline, and ghs/qol from baseline. (Phase ?); | — |
Countries
China
Contacts
Public ContactZiming Li
Shanghai Chest Hospital
Outcome results
None listed